We propose a new paradigm for ultrasound wave analysis in order to non-invasively compute mechanical properties (nonlinear stiffness) and functional strains in ligaments and tendons. Mechanical properties can diagnose damage or a pathologic state (i.e. tendonitis or tendinosis) and it can quantify the extent of healing. Tissue strains indicate functional loadings for rehabilitation and recovery. If successful, our method will significantly improve upon existing methods and find numerous applications that benefit public health. And, it will provide an improved tool for scientific inquiry in many musculoskeletal studies of relevance to NIAMS. This study applies acoustoelasticity (AE) to biomedical ultrasound imaging for the first time. AE is a mathematical theory that rigorously describes ultrasonic wave propagation in deformed elastic materials, interrelating reflected waves to mechanical properties and strain. After a tissue such as tendon or ligament is stretched (i.e. functionally loaded), AE models wave propagation in a deformed medium more accurately than existing methods. Currently, other ultrasound-based methods use "wave theory", which does not account for deformation-dependent changes in wave velocity and amplitude. Preliminary studies clearly show that "wave theory" analysis can cause significant errors when ultrasound is used to compute tissue properties. AE analysis has the potential to: 1) avoid these errors, 2) include tissue non-linearities, 3) acquire all requisite data with one functional loading, and 4) compute strain and mechanical properties in virtually real time. This technique does not require additional force measurements or time-consuming numerical modeling to extract properties. To our knowledge, no existing method can evaluate both applied strain and nonlinear tissue properties simultaneously in virtually real time. This study will test the efficacy of an AE-based technique termed "Acoustoelastic Strain Gauge" (ASG) on animal tendons (tendons in rat and pig limbs after sacrifice). Tendons will be analyzed in situ, that is, through skin and superficial tissues while being stretched with a mechanical test system. In this study ASG will be applied to porcine flexor tendons (intact and with induced subfailure damage to simulate various levels of 2nd degree sprains). ASG will be applied to rat Achilles tendons (intact and after surgical rupture and various periods of healing). In both animal models, applied strain and strain-dependent tissue properties of the in situ stretched tendons will be evaluated. Strain from ASG will be correlated with strain from a mechanical test system to demonstrate accuracy and repeatability of the ASG technique. This study will determine the ability and sensitivity of ASG to quantify the level of sub-failure damage (as determined by a reduction in ultimate force). Finally, this study will determine the ability of ASG to predict strength recovery during healing. PUBLIC HEALTH RELEVANCE: We propose a new and different method of ultrasound wave analysis to non-invasively measure mechanical properties and functional strains in soft tissues. If successful, this new diagnostic tool be a significant improvement over existing methods and will find numerous applications that benefit public health. Consider, for example, functional strain measurement. In the U.S. more than 12 million people visited orthopedic surgeons in 2003 because of either knee or shoulder problems. Knee ligament injuries are common, and almost all shoulder problems are related to stretched or ruptured tissues with altered functional loads. Consider, for example, mechanical property identification. The American Cancer Society estimated in 2005 that approximately 211,240 women were diagnosed with invasive breast cancer in the U.S. and 232,090 men were diagnosed with prostate cancer. Clearly, non-invasive tissue strain to measure functional loads and non-invasive mechanical properties to distinguish and identify tissue types would be valuable. Our method has the potential to improve upon existing methods in these areas. A recent study in a Medicare population projected that musculoskeletal imaging costs in 2020 will be $3.6 billion, of which $2 billion will be for MRI. Investigators estimated 45% of the MRI diagnoses could have been made with ultrasound, and if appropriately substituted, could result in cost savings of nearly $7 billion over the next 14 years. Innovative developments in ultrasound technology may create value added features resulting in increased interest and significant.